095 - The Agglutinative Reaction in Relation to Pertussis and to Prophylactic Vaccination against Pertussis with Description of a New Technic

One big question is whether you can tell if someone is immune to a disease (with methods other than exposing them and seeing if they get sick, of course). Often antibody levels are used as a proxy for immunity in the absence of an epidemic or something. This study looks at antibodies to whooping cough that cause agglutination (clumping together of cellular material) and seeing if that correlates with immunity and such. It would make the test easier than the ones that were done at the time, at least, though those might've been more reliable.

So they tested 101 children that had never had pertussis or vaccination against it. Ten of them showed some agglutination.

164 others were vaccinated with killed bacteria. All but 3 showed high levels of agglutination, much higher than the 10 negative controls.

Finally, 71 children during or after an infection with pertussis were tested. The titers were lower than after vaccination, but of those tested during, 15 out of 17 had agglutination, and 36 of 67 had it after their coughing stopped. Titers went down over the several months following the disease.

So it seemed like agglutination correlates well with vaccination status, but not so well with actual infection history. So it's not clear how useful it actually is, as far as I can tell. Maybe having high levels is indicative of immunity, but having low levels doesn't always mean lack of immunity, but it's not conclusive yet.

Reference:

Miller, Jr, J. J. & Silverberg, R. J. The Agglutinative Reaction in Relation to Pertussis and to Prophylactic Vaccination against Pertussis with Description of a New Technic. J Immunol 37, 207–221 (1939).

094 - Active Immunization Against Whooping-Cough

This study has two parts, both relating to whooping cough vaccination. The first seems like a brief summary of a clinical trial, and the second is an animal trial testing which method of killing pertussis bacteria makes the best vaccine.

Part I
This was more exciting, and thus unfortunately lacking in details. There were 288 vaccinated and 1007 control children, followed by questionnaires to parents and physicians. There were 52 known exposures of controls to disease, and 97 exposures in the vaccinated group. From these exposures, 43 resulted in disease in controls, and 10 in vaccinated. This means 82% infection rate in controls, and 10% in vaccinated, meaning 72% protection from the vaccine. That's pretty good.

Also worth mentioning was that 23 of the 97 vaccinated exposures were intimate, meaning siblings that shared a bed or played together or whatever, but none of these resulted in disease in the vaccinated child.

So pretty good, but lacking in necessary details.

Part II
This was a study in mice using vaccines made of killed bacteria, but killed in different ways: phenol, formalin (formaldehyde), merthiolate (thimerosal), or heat. They tried increasing doses of each in mice before challenging with pertussis to see how many died. They found that phenol-killed vaccine required the lowest dose to start showing protection, followed by heat-killed. The others were worse.

The dose required to show any protection, relative to the weight of the mice, was very high, but this could be explained by the requirement that mice be able to resist a serious bacterial infection (the bacteria are injected into their body cavity), rather than a simple respiratory exposure, so it's probably not comparable to humans, in dose at least.

Reference:

Silverthorne, N. Active Immunization Against Whooping-Cough. Can Med Assoc J 41, 263–265 (1939).

093 - H. pertussis Vaccines: The Effect of Washing and the Use of Mouse Protection Tests

In previous studies of whooping cough vaccines, most showed protection but a few did not, and it wasn't really clear why these studies were negative. One hypothesis was that while preparing the vaccine for these negative studies, a washing step was included that made the vaccine ineffective. So this study investigated this question by trying different preparation methods and testing the results on mice.

The three preparations were unwashed, washed with distilled water, or washed with saline. The protein observed in the washing liquid was similar between the two kinds, and didn't seem to have much toxicity or antigenicity, at least not for mice.

So then they tested the vaccines themselves with mice. It took a few trials before they got a really good protocol for mouse protection trials, with the unwashed vaccine giving good protection and the infection challenge being strong enough to kill most of the controls. Eventually they succeeded though. But none of the trials seemed to consistently show a significant difference between types of washing, or washed vs. unwashed.

So the reason the negative trials were negative is still a mystery, sadly. But at least future studies had a decent protocol for testing pertussis vaccines with mice, which seems to be the main reason they cite this study.

Reference:

Miller, Jr., J. J. & Silverberg, R. J. H. pertussis Vaccines: The Effect of Washing and the Use of Mouse Protection Tests. The Journal of Infectious Diseases 65, 16–23 (1939).